China is the world’s largest producer and consumer of aquatic products. Insecticides， as well as veterinary drugs， such as quinolones， macrolides， nitroimidazoles， sulfonamides， and amphenicols， are widely used in aquaculture. These compounds play crucial roles in preventing， controlling， and treating diseases in aquatic organisms， improving feed conversion rates， and promoting the healthy growth of farmed species. However， the illegal use of veterinary drugs， their overuse， and noncompliance with drug withdrawal periods by farmers can lead to aquatic products containing veterinary drug residues. This study focused on fish， shrimp， and crabs with the aim of meeting the green-development needs of China’s aquaculture industry， strengthening risk warnings and preventing veterinary drug residues in aquatic products， enhancing the quality and competitiveness of farmed aquatic products， and promoting the sustainable development of the aquaculture industry. Instrumental working conditions were optimized， and the extraction solvent， extraction method， purification materials， and the redissolution solvent used in the sample-pretreatment process were determined. These efforts led to the establishment of a protocol for the detection of 50 veterinary drug residues， including quinolones， macrolides， nitroimidazoles， sulfonamides， amphenicols， and insecticides， in fish， shrimp， and crabs， which involved one-step pretreatment with a composite purification column in combination with ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS）. A 5-g sample was extracted with a 1.0% acetic acid solution， dehydrated with anhydrous sodium sulfate， and purified using a FAVEX purification column， after which the purified solution was nitrogen-blown to near dryness. The residue was re-dissolved in 1.0 mL of 0.2% formic acid aqueous solution-methanol （9∶1， v/v） ， filtered， and then separated using a Waters ACQUITY UPLC^® BEH C18 column （100 mm × 2.1 mm， 1.7 μm）. Data were collected in positive- and negative-ion multiple reaction monitoring modes， and quantified using isotopic internal and external standards. All target compounds exhibited good linear relationships within their respective concentration ranges， with coefficients of determination （R²） greater than 0.990 0. Average recovery rates of 60.1%–117.8% were determined for the 50 veterinary drugs in the fish matrix， with RSDs of between 1.89% and 15.0%， while the shrimp matrix delivered average recovery rates of 60.2%–119.7%， with RSDs of 1.11%–15.6%， and the crab matrix exhibited average values of 60.7%–119.7% and 2.94%–15.0%， respectively. The developed method is advantageous owing to its simple pretreatment step， high throughput， low organic-solvent consumption， good accuracy， high sensitivity， and cost-effectiveness. One hundred and fifty batches of aquatic products， including 50 batches of fish， 50 batches of shrimp， and 50 batches of crab， were risk-screened for 50 veterinary drug residues using the established detection method. Veterinary drug residues were detected at a rate of 47.3%， with an over-standard rate of 7.3%. Specifically， the fish samples exhibited a detection rate of 66.0%， with contamination concentrations of 1.20–257.1 μg/kg. In contrast， the shrimp samples exhibited a detection rate of 18.0%， with contamination concentrations of 1.10–8.60 μg/kg， while values of 22.0% and 3.00–7.30 μg/kg， respectively， were determined for the crab samples. This study identified a total of seven veterinary drug residues， namely pefloxacin， norfloxacin， ciprofloxacin， enrofloxacin， sarafloxacin， sulfadimethoxine， and sulfamethoxazole， with detection rates of 0.67%， 5.3%， 12.7%， 20.7%， 4.6%， 2.00%， and 1.33%， respectively. The detection method established in this study provides strong technical support for monitoring and assessing aquatic-product risks in a timely manner， and is expected play an important role in ensuring food safety， protecting consumer health， and promoting the healthy development of the aquatic-product industry.